Reactive processing of polymers: structural characterization of products by 1H and 13C NMR spectroscopy for glycidyl methacrylate grafting onto EPR in the absence and presence of a reactive comonomer

Grafted GMA on EPR samples were prepared in a Thermo-Haake internal mixer by free radical melt grafting reactions in the absence (conventional system; EPR-g-GMA(CONV)) and presence of the reactive comonomer divinyl benzene, DVB (EPR-g-GMA(DVB)). The GMA-homopolymer (poly-GMA), a major side reaction product in the conventional system, was almost completely absent in the DVB-containing system, the latter also resulted in a much higher level of GMA grafting. A comprehensive microstructure analysis of the formed poly-GMA was performed based on one-dimensional H-1 and C-13 NMR spectroscopy and the complete spectral assignments were supported by two-dimensional NMR techniques based on long range two and three bond order carbon-proton couplings from HMBC (Heteronuclear Multiple Bond Coherence) and that of one bond carbon-proton couplings from HSQC (Heteronuclear Single Quantum Coherence), as well as the use of Distortionless Enhancement by Polarization Transfer (DEPT) NMR spectroscopy. The unambiguous analysis of the stereochemical configuration of poly-GMA was further used to help understand the microstructures of the GMA-grafts obtained in the two different free radical melt grafting reactions, the conventional and comonomer-containing systems. In the grafted GMA, in the conventional system (EPR-g-GMA(CONV)), the methylene protons of the GMA were found to be sensitive to tetrad configurational sequences and the results showed that 56% of the GMA sequence in the graft is in atactic configuration and 42% is in syndiotactic configuration whereas the poly-GMA was predominantly syndiotactic. The differences in the microstructures of the graft in the conventional EPR-g-GMA(CONV) and the DVB-containing (EPR-g-GMA(DVB)) systems is also reported (C) 2009 Elsevier Ltd. All rights reserved.

Gold nanoparticles decorated with oligo(ethylene glycol) thiols:kinetics of colloid aggregation driven by depletion forces

We have studied the kinetics of the phase-separation process of mixtures of colloid and protein in solutions by real-time UV-vis spectroscopy. Complementary small-angle X-ray scattering (SAXS) was employed to determine the structures involved. The colloids used are gold nanoparticles functionalized with protein resistant oligo(ethylene glycol) (OEG) thiol, HS(CH(2))(11)(OCH(2)CH(2))(6)OMe (EG6OMe). After mixing with protein solution above a critical concentration, c*, SAXS measurements show that a scattering maximum appears after a short induction time at q = 0.0322 angstrom(-1) stop, which increases its intensity with time but the peak position does not change with time, protein concentration and salt addition. The peak corresponds to the distance of the nearest neighbor in the aggregates. The upturn of scattering intensities in the low q-range developed with time indicating the formation of aggregates. No Bragg peaks corresponding to the formation of colloidal crystallites could be observed before the clusters dropped out from the solution. The growth kinetics of aggregates is followed in detail by real-time UV-vis spectroscopy, using the flocculation parameter defined as the integral of the absorption in the range of 600-800 nm wavelengths. At low salt addition (<0.5 M), a kinetic crossover from reaction-limited cluster aggregation (RLCA) to diffusion-limited cluster aggregation (DLCA) growth model is observed, and interpreted as being due to the effective repulsive interaction barrier between colloids within the depletion potential. Above 0.5 M NaCl, the surface charge of proteins is screened significantly, and the repulsive potential barrier disappeared, thus the growth kinetics can be described by a DLCA model only.

A sulphonate based hydrogel for nucleus pulposus repair

Introduction: Lower back pain treatment and compensation costs >$80 billion overall in the US. 75% of back pain is due to disc degeneration in the lumbar region of the spine. Current treatment comprises of painkillers and bed rest or as a more radical solution – interbody cage fusion. In the early stages of disc degeneration the patient would benefit from addition of an injectable gel which polymerises in situ to support the degenerated nucleus pulposus. This involves a material which is an analogue of the natural tissue capable of restoring the biomechanical properties of the natural disc. The nucleus pulposus of the intervertebral disc is an example of a natural proteoglycan consisting of a protein core with negatively charged keratin and chondroitin sulphate attached. As a result of the high fixed charge density of the proteoglycan, the matrix exerts an osmotic swelling pressure drawing sufficient water into support the spinal system. Materials and Methods: NaAMPs (sodium 2- acrylamido 2-methyl propane sulphonic acid) and KSPA (potassium 3- sulphopropyl acrylate) were selected as monomers, the sulphonate group being used to mimic the natural sulphate group. These are used in dermal applications involving chronic wounds and have acceptably low cytotoxicity. Other hydrophilic carboxyl, amide and hydroxyl monomers such as 2-hydroxyethyl acrylamide, ß-carboxyethyl acrylate, acryloyl morpholine, and polyethylene glycol (meth)acrylate were used as diluents together with polyethyleneglycol di(meth)acrylate and hydrophilic multifunctional macromers as cross-linker. Redox was the chosen method of polymerisation and a range of initiators were investigated. Components were packaged in two solutions each containing a redox pair. A dual syringe method of injection into the cavity was used, the required time for polymerisation is circa 3-7 minutes. The final materials were tested using a Bohlin CVO Rheometer cycling from 0.5-25Hz at 37oC to measure the modulus. An in-house compression testing method was developed, using dialysis tubing to mimic the cavity, the gels were swelled in solutions of various osmolarity and compressed to ~ 20%. The pre-gel has also been injected into sheep spinal segments for mechanical compression testing to demonstrate the restoration of properties upon use of the gel. Results and Discussion: Two systems resulted using similar monomer compositions but different initiation and crosslinking agents. NaAMPs and KSPA were used together at a ratio of ~1:1 in both systems with 0.25-2% crosslinking agent, diacrylate or methacrylate. The two initiation systems were ascorbic acid/oxone, and N,N,N,N - tetramethylethylenediamine (TEMED)/ potassium persulphate. These systems produced gelation within 3-7 and 3-5 minutes respectively. Storage of the two component systems was shown to be stable for approximately one month after mixing, in the dark, refrigerated at 1-4oC. The gelation was carried out at 37oC. Literature values for the natural disc give elastic constants ranging from 3-8kPa. The properties of the polymer can be tailored by altering crosslink density and monomer composition and are able to match those of the natural disc. It is possible to incorporate a radio-opaque (histodenz) to enable x-ray luminescence during and after injection. At an inclusion level of 5% the gel is clearly visible and polymerisation and mechanical properties are not altered. Conclusion: A two-pac injection system which will polymerise in situ, that can incorporate a radio-opaque, has been developed. This will reinforce the damaged nucleus pulposus in degenerative disc disease restoring adequate hydration and thus biomechanical properties. Tests on sheep spine segments are currently being carried out to demonstrate that a disc containing the gel has similar properties to an intact disc in comparison to one with a damaged nucleus.

Reactive processing of polymers:effect of bifunctional and tri-functional comonomers on melt grafting of glycidyl methacrylate onto polypropylene

Two reactive comonomers, divinyl benzene (DVB) and trimethylolpropane triacrylate (TRIS), were evaluated for their role in effecting the melt free radical grafting reaction of the monomer glycidyl methacrylate (GMA) onto polypropylene (PP). The characteristics of the GMA-grafting systems in the presence and absence of DVB or TRIS were examined and compared in terms of the yield of the grafting reaction and the extent of the main side reactions, namely homopolymerisation of GMA (poly-GMA) and polymer degradation, using different chemical compositions of the reactive systems and processing conditions. In the absence of the comonomers, i.e. in a conventional system, high initiator concentrations of peroxides were typically required to achieve the highest possible GMA grafting levels which were found to be generally low. Concomitantly, both poly-GMA and degradation of the polymer by chain scission takes place with increasing initiator amounts. On the other hand, the presence of a small amount of the comonomers, DVB or Tris, in the GMA-grafting system, was shown to bring about a significant increase in the grafting level paralleled by a large reduction in poly-GMA and PP degradation. In the presence of these highly reactive comonomers, the optimum grafting system requires a much lower concentration of the peroxide initiator and, consequently, would lead to the much lower degree of polymer degradation observed in these systems. The differences in the effects of the presence of DVB and that of TRIS in the grafting systems on the rate of the GMA-grafting and homopolymerisation reactions, and the extent of PP degradation (through melt flow changes), were compared and contrasted with a conventional GMA-grafting system.

Fabrication and characterization of macroporous poly(ethylene glycol) hydrogels generated by several types of porogens

Polymer scaffolds play an important role in tissue engineering applications. Poly(ethylene glycol) based hydrogels have received a lot of attention in this field because of their high biocompatibility and ease of processing. However, in many cases they do not exhibit proper tissue invasion and nutrient transport because of their dense structure. In the present work, several approaches were developed and compared to each other to produce interconnected macroporous poly(ethylene glycol) hydrogels by including different types of porogens in the photocrosslinking reaction. The swelling capacity of the resulting hydrogels was analyzed and compared to non-porous hydrogel samples. Moreover, the obtained materials were characterized by means of mechanical properties and porosity using rheometry, scanning electron microscopy, and mercury intrusion porosimetry. Results showed that interconnected and uniform pores were obtained when a porogen template was used during hydrogel fabrication by photocrosslinking. On the other side, when the porogen particles were dispersed into the macromer solution before matrix photocrosslinking the interconnexion was negligible. The templates must be dissolved before the hydrogel's cell-seeding in vitro, while the dispersed porogen can be used in situ in the in vitro seeding tests. Copyright © 2013 Taylor & Francis Group, LLC.

Structural effects in photopolymerized sodium AMPS hydrogels crosslinked with poly(ethylene glycol) diacrylate for use as burn dressings

Synthetic hydrogel polymers were prepared by free radical photopolymerization in aqueous solution of the sodium salt of 2-acrylamido-2-methylpropane sulfonic acid (Na-AMPS). Poly(ethylene glycol) diacrylate (PEGDA) and 4,4'-azo-bis(4-cyanopentanoic acid) were used as the crosslinker and UV-photoinitiator, respectively. The effects of varying the Na-AMPS monomer concentration within the range of 30-50% w/v and the crosslinker concentration within the range of 0.1-1.0% mol (relative to monomer) were studied in terms of their influence on water absorption properties. The hydrogel sheets exhibited extremely high swelling capacities in aqueous media which were dependent on monomer concentration, crosslink density, and the ionic strength and composition of the immersion medium. The effects of varying the number-average molecular weight of the PEGDA crosslinker from = 250 to 700 were also investigated. Interestingly, it was found that increasing the molecular weight and therefore the crosslink length at constant crosslink density decreased both the rate of water absorption and the equilibrium water content. Cytotoxicity testing by the direct contact method with mouse fibroblast L929 cells indicated that the synthesized hydrogels were nontoxic. On the basis of these results, it is considered that photopolymerized Na-AMPS hydrogels crosslinked with PEGDA show considerable potential for biomedical use as dressings for partial thickness burns. This paper describes some structural effects which are relevant to their design as biomaterials for this particular application. © 2013 Copyright Taylor and Francis Group, LLC.

Highly photosensitive polymethyl methacrylate microstructured polymer optical fiber with doped core

In this Letter, we report the fabrication of a highly photosensitive, microstructured polymer optical fiber using benzyl dimethyl ketal as a dopant, as well as the inscription of a fiber Bragg grating in the fiber. A refractive index change in the core of at least 3.2 × 10 has been achieved, providing a grating with a strong transmission rejection of -23 dB with an inscription time of only 13 min. The fabrication method has a big advantage compared to doping step index fiber since it enables doping of the fiber without using extra dopants to compensate for the index reduction in the core introduced by the photosensitive agent. © 2013 Optical Society of America.

Photosensitivity mechanism of undoped poly(methyl methacrylate) under UV radiation at 325 nm and its spatial resolution limit

In this Letter, we provide evidence suggesting that the main photosensitive mechanism of an undoped poly(methyl methacrylate)-based microstructured optical fiber under UV radiation at 325 nm is a competitive process of both photodegradation and polymerization. We found experimentally that increasing strain during photo-inscription leads to an increased photosensitivity, which is evidence of photodegradation. Likewise, refractive index change in the fiber was measured to be positive, which provides evidence for further polymerization of the material. Finally, we relate the data obtained to the spatial recording resolution of the samples. © 2014 Optical Society of America.

Gold nanoparticles decorated with oligo(ethylene glycol) thiols:protein resistance and colloidal stability

The interactions between proteins and gold colloids functionalized with protein-resistant oligo(ethylene glycol) (OEG) thiol, HS(CH(2))(11) (OCH(2)CH(2))(6)OMe (EG(6)OMe), in aqueous solution have been studied by small-angle X-ray scattering (SAXS) and UV-vis spectroscopy. The mean size, 2R, and the size distribution of the decorated gold colloids have been characterized by SAXS. The monolayer-protected gold colloids have no correlations due to the low volume fraction in solution and are stable in a wide range of temperatures (5-70 degrees C, pH (1.3-12.4), and ionic strength (0-1.0 M). In contrast, protein (bovine serum albumin) solutions with concentrations in the range of 60-200 mg/mL (4.6-14.5 vol show a pronounced correlation peak in SAXS, which results from the repulsive electrostatic interaction between charged proteins. These protein interactions show significant dependence on ionic strength, as would be expected for an electrostatic interaction (Zhang et al. J. Phys. Chem. B 2007, 111, 251). For a mixture of proteins and gold colloids, the protein-protein interaction changes little upon mixing with OEG-decorated gold colloids. In contrast, the colloid-colloid interaction is found to be strongly dependent on the protein concentration and the size of the colloid itself. Adding protein to a colloidal solution results in an attractive depletion interaction between functionalized gold colloids, and above a critical protein concentration, c*, the colloids form aggregates and flocculate. Adding salt to such mixtures enhances the depletion effect and decreases the critical protein concentration. The aggregation is a reversible process (i.e., diluting the solution leads to dissolution of aggregates). The results also indicate that the charge of the OEG self-assembled monolayer at a curved interface has a rather limited effect on the colloidal stabilization and the repulsive interaction with proteins.

Humidity responsivity of poly(methyl methacrylate)-based optical fiber Bragg grating sensors

The humidity response of poly(methyl methacrylate) (PMMA)-based optical fiber Bragg gratings (POFBGs) has been studied. The characteristic wavelength of the grating is modulated by water absorption-induced swelling and refractive index change in the fiber. This work indicates that anisotropic expansion may exist in PMMA optical fiber, reducing the humidity responsivity of the grating and introducing uncertainty in the responsivity from fiber to fiber. By pre-straining a grating, one can get rid of this uncertainty and simultaneously improve the POFBG response time. © 2014 Optical Society of America.

Controlled growth of poly(2-(diethylamino)ethyl methacrylate) brushes via atom transfer radical polymerisation on planar silicon surfaces

Progress in making pH-responsive polyelectrolyte brushes with a range of different grafting densities is reported. Polymer brushes of poly(2-(diethylamino)ethyl methacrylate) were synthesised via atom transfer radical polymerisation on silicon wafers using a 'grafted from' approach. The [11-(2-bromo-2-methyl) propionyloxy]undecyl trichlorosilane initiator was covalently attached to the silicon via silylation, from which the brushes were grown using a catalytic system of copper(I) chloride and pentamethyldiethylenetriamine in tetrahydrofuran at 80°C. X-ray reflectivity was used to assess the initiator surfaces and an upper limit on the grafting density of the polymer was determined. The quality of the brushes produced was analysed using ellipsometry and atomic force microscopy, which is also discussed.

Proplyene glycol intake from medications used on paediatric intensive care

here is an increasing number of reports of propylene glycol (PG) toxicity in the literature, regardless of its inclusion on the Generally Recognized as Safe List (GRAS).1 PG is an excipient used in many medications as a solvent for water-insoluble drugs. Polypharmacy may increase PG exposure in vulnerable PICU patients who may accumulate PG due to compromised liver and renal function. The study aim was to quantify PG intake in PICU patients and attitudes of clinicians towards PG. Method A snapshot of 50 PICU patients oral or intravenous medication intake was collected. Other data collected included age, weight, diagnosis, lactate levels and renal function. Manufacturers were contacted for PG content and then converted to mg/kg. Excipients in formulations that compete with the PG metabolism pathway were recorded. The Intensivists' opinions on PG intake was sought via e-survey. Results The 50 patients were prescribed 62 drugs and 83 formulations, 43/83 (52%) were parenteral formulations. Median weight of the patients was 5.5 kg (range 2–50 kg), ages ranged from 1 day to 13 years of age. Eleven of the patients were classed as renally impaired (defined as 1.5 times the baseline creatinine). Sixteen formulations contained PG, 2/16 were parenteral, 6/16 unlicensed preparations. Thirty-eight patients received at least one prescription containing PG and 29/38 of these patients were receiving formulations that contained excipients that may have competed with the metabolic pathways of PG. PG intake ranged from 0.002 mg/kg/day to 250 mg/kg/day. Total intake was inconclusive for 2 patients due to a of lack of availability of information from the manufacturer; these formulations were licensed but used in for off-label indications. Five commonly used formulations contributed to higher intakes of PG, namely co-trimoxazole, dexamethasone, potassium chloride, dipyridamole and phenobarbitone. Lactate levels were difficult to interpret due to the underlying conditions of the patients. One of the sixteen intensivist was aware of PG content in drugs, 16/16 would actively change therapy if intake was above European Medicines Agency recommendations. Conclusions Certain formulations used on PICU can considerably increase PG exposure to patients. Due to a lack of awareness of PG content, these should be highlighted to the clinician to assist with making informed decisions regarding risks versus benefits in continuing that drug, route of administration or formulation.

Proplyene glycol intake from medications used on paediatric intensive care

There is an increasing number of reports of propylene glycol (PG) toxicity in the literature, regardless of its inclusion on the Generally Recognized as Safe List (GRAS).1 PG is an excipient used in many medications as a solvent for water-insoluble drugs. Polypharmacy may increase PG exposure in vulnerable PICU patients who may accumulate PG due to compromised liver and renal function. The study aim was to quantify PG intake in PICU patients and attitudes of clinicians towards PG. Method A snapshot of 50 PICU patients oral or intravenous medication intake was collected. Other data collected included age, weight, diagnosis, lactate levels and renal function. Manufacturers were contacted for PG content and then converted to mg/kg. Excipients in formulations that compete with the PG metabolism pathway were recorded. The Intensivists' opinions on PG intake was sought via e-survey. Results The 50 patients were prescribed 62 drugs and 83 formulations, 43/83 (52%) were parenteral formulations. Median weight of the patients was 5.5 kg (range 2–50 kg), ages ranged from 1 day to 13 years of age. Eleven of the patients were classed as renally impaired (defined as 1.5 times the baseline creatinine). Sixteen formulations contained PG, 2/16 were parenteral, 6/16 unlicensed preparations. Thirty-eight patients received at least one prescription containing PG and 29/38 of these patients were receiving formulations that contained excipients that may have competed with the metabolic pathways of PG. PG intake ranged from 0.002 mg/kg/day to 250 mg/kg/day. Total intake was inconclusive for 2 patients due to a of lack of availability of information from the manufacturer; these formulations were licensed but used in for off-label indications. Five commonly used formulations contributed to higher intakes of PG, namely co-trimoxazole, dexamethasone, potassium chloride, dipyridamole and phenobarbitone. Lactate levels were difficult to interpret due to the underlying conditions of the patients. One of the sixteen intensivist was aware of PG content in drugs, 16/16 would actively change therapy if intake was above European Medicines Agency recommendations. Conclusions Certain formulations used on PICU can considerably increase PG exposure to patients. Due to a lack of awareness of PG content, these should be highlighted to the clinician to assist with making informed decisions regarding risks versus benefits in continuing that drug, route of administration or formulation.

Synthesis, self-assembly and (absence of) protein interactions of poly(glycerol methacrylate)-silicone macro-amphiphiles

The present study focuses on the synthesis of amphiphilic block copolymers containing poly(glycerol monomethacrylate) (PGMMA), showing the advantages of a protection/deprotection strategy based on silyl groups. PGMMA blocks were synthesized via ATRP started by a double functional poly(dimethyl siloxane) (PDMS) macroinitiator of molecular weight ≈7000 g mol-1. The resulting triblock copolymers were characterized by low polydispersity (generally ≤1.1) and their aggregation concentration in water was essentially dominated by the PDMS block length (critical aggregation concentration substantially invariant for GMMA degree of polymerization ≥30). For GMMA blocks with DP > 50, the self-assembly in water produced 35-50 nm spherical micelles, while shorter hydrophilic chains produced larger aggregates apparently displaying worm-like morphologies. Block copolymers with long GMMA chains (DP ≈ 200) produced particularly stable micellar aggregates, which were then selected for a preliminary assessment of the possibility of adsorption of plasma proteins (albumin and fibrinogen); using diffusion NMR as an analytical technique, no significant adsorption was recorded both on micelles and on soluble PGMMA employed as a control, indicating the possibility of a "stealth" behaviour. This journal is © 2013 The Royal Society of Chemistry.